Analgesia induced by several general anesthetic agents is partially antagonized by the specific narcotic antagonists, naloxone and naltrexone. These observations in experimental animals suggest a possible mechanism of anesthesia involving interactions between anesthetics and the opiate receptor-endorphin system. Other similarities between the actions of narcotics and general anesthetics were also found. We seek more direct biochemical evidence in support of this hypothesis, for which a body of indirect pharmacologic evidence already exists. We propose to study the influence of general anesthetics upon the binding of ligands (narcotics, narcotic antagonists and endorphins) to opiate receptors present in brain both in vivo, using pulse-labeling techniques, and in vitro, using binding assays. Using bioassays, the effects of anesthetics on dose-response relationships of narcotics will be examined. We also propose to measure endorphin concentrations in brain regions in rat exposed to general anesthetics and compare these with rats in the awake state, using bioassay, radioligand binding assay, and specific radioimmunoassay for met5-enkephalin. The effect of anesthetics on endorphin concentrations in cerebrospinal fluid of dogs will be studied as well.